JAMA Neurol. 2026 Feb 2:e255496. doi: 10.1001/jamaneurol.2025.5496. Online ahead of print.
ABSTRACT
IMPORTANCE: Ipsilesional upper-limb motor deficits after stroke are functionally important yet largely neglected in rehabilitation. Remediation may improve motor outcomes in individuals with severe contralesional arm hemiparesis.
OBJECTIVE: To determine whether training of the ipsilesional arm improves motor performance in chronic stroke with severe contralesional impairment and significant ipsilesional arm motor deficits.
DESIGN, SETTING, AND PARTICIPANTS: This 2-site, parallel-group randomized clinical trial with blinded outcome assessment was conducted from February 2019 to August 2024, with follow-up through 6 months posttreatment. Data analysis was performed from August 2024 through August 2025. The trial was conducted at outpatient research laboratories at Penn State College of Medicine and the University of Southern California among adults with radiologically confirmed unilateral middle cerebral artery stroke, severe contralesional upper-extremity impairment (Fugl-Meyer score ≤28), and ipsilesional motor deficits. Participants were randomly assigned with equal probability to 2 treatment groups and stratified by sex.
INTERVENTIONS: Participants were randomized to a 5-week, 15-session intervention focused on either the ipsilesional (n = 25) or contralesional (n = 28) upper limb. The ipsilesional group received ipsilesional virtual reality and manipulation training; the contralesional group received dose-matched, best practice contralesional arm therapy.
MAIN OUTCOMES AND MEASURES: The primary outcomes were ipsilesional motor performance (Jebsen-Taylor Hand Function Test [excluding writing]), functional independence (Barthel Index), contralesional impairment severity (Fugl-Meyer Assessment [Upper Extremity]), and perceived manual ability (ABILHAND-Stroke).
RESULTS: Of 100 adults screened, 58 were included, and 53 participants (91%) completed both baseline and immediate posttreatment assessments. Of the 53 participants who completed the study, mean (SD) age was 59 (11) years, and 17 participants (32%) were female. In this modified intent-to-treat analysis, the ipsilesional treatment group showed significant improvement in Jebsen-Taylor Hand Function Test performance (mean difference, -5.87 seconds; 95% CI, -8.89 to -2.85 seconds; P = .003), representing a 12% reduction in time to completion. Relative to its own baseline, this improvement was sustained at the 3-week and 6-month follow-up times within the ipsilesional treatment group only. No significant effects were observed for the remaining outcomes.
CONCLUSIONS AND RELEVANCE: In this parallel-group randomized clinical trial, targeted ipsilesional arm training significantly improved ipsilesional motor performance in patients with chronic stroke with severe paresis. This approach may enhance functional capacity in patients who rely on the ipsilesional arm for daily activities.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03634397.
PMID:41627841 | PMC:PMC12865693 | DOI:10.1001/jamaneurol.2025.5496